Anitha Kilari

Fatty acids, antioxidants, and oxidative stress in pre-eclampsia

To investigate whether free radical‐mediated membrane lipid peroxidation may be implicated in the pathogenesis of pre‐eclampsia.

Circulating angiogenic factors and their association with birth outcomes in preeclampsia

This study was designed to test the hypothesis that altered angiogenic factors together with increased oxidative stress and reduced docosahexaenoic acid (DHA) levels may be associated with altered birth outcome parameters. To test this hypothesis, levels of plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), the oxidative stress marker malondialdehyde (MDA) and fatty acids were estimated in women with preeclampsia and their cord samples and compared with those in normotensive women. The association of these parameters with birth outcome was also examined. Our results show that in preeclamptic women, maternal plasma VEGF and PlGF levels were lower, whereas sFlt-1 levels were higher (P<0.05 for all) than in normotensive women. In contrast, cord plasma VEGF levels were higher (P<0.05) in preeclamptic women, whereas there was no difference in sFlt-1 levels. Plasma DHA levels in both the mother and cord were lower (P<0.05) in the preeclamptic group compared with normotensive women. Maternal plasma sFlt-1 levels were positively (n=23, r=0.415, P=0.039) associated with MDA concentrations in preeclamptic women. Maternal plasma sFlt-1 levels showed a strong negative association with baby weight (n=37, r=−0.547, P=0.001), head circumference (n=37, r=−0.472, P=0.005) and baby chest circumference (n=37, r=−0.375, P=0.032) in the preeclamptic group. Cord plasma sFlt-1 concentrations were negatively associated with cord plasma DHA concentrations (n=28, r=−0.552, P=0.004). This study suggests that dysregulation of angiogenic factors may be associated with maternal oxidative stress. Increased oxidative stress may reduce cord DHA levels and increase sFlt-1 levels, leading to poor birth outcomes in preeclampsia.

Association of omega-3 fatty acids and homocysteine concentrations in pre-eclampsia.

BACKGROUND & AIMSnThe present study examines the associations of folic acid, vitamin B₁₂ and omega-3 fatty acids and increased homocysteine which are implicated in the pathology of pre-eclampsia.nnnMETHODSn49 Pre-eclamptic and 57 normotensive women were recruited at Bharati hospital, Pune, India. Plasma folate, vitamin B₁₂, homocysteine and erythrocyte omega-3 and omega-6 fatty acids were analyzed.nnnRESULTSnHomocysteine concentrations were higher in pre-eclamptic than in normotensive women (14.28±7.31 vs. 11.03±4.38 μmol/l, p<0.01) despite similar levels of folic acid and vitamin B₁₂. In the pre-eclamptic group, plasma folate levels were positively associated with erythrocyte omega-6 fatty acids (p<0.05) while erythrocyte docosahexaenoic acid levels were negatively associated with plasma homocysteine levels (p<0.01).nnnCONCLUSIONSnOur study provides evidence for the associations of altered omega-3 fatty acids especially docosahexaenoic acid and the resultant increased homocysteine concentrations in pre-eclampsia. Future studies need to examine if docosahexaenoic acid supplementation during pregnancy reduces homocysteine levels and ameliorates the risk of developing pre-eclampsia.

Long chain polyunsaturated fatty acids in mothers and term babies

Abstract Aim: To establish the levels of docosahexaenoic acid (DHA) and arachidonic acid (AA) in both plasma and erythrocytes of maternal and cord blood as well as in breast milk of mothers delivering babies at term. Methods: A total of 148 mothers delivering babies at term were recruited from Bharati Medical Hospital, Pune, India. Results: Levels of DHA and AA in both plasma and erythrocyte were higher in cord blood compared to levels in maternal blood (P<0.001). Maternal plasma and erythrocyte DHA levels had a positive association with the respective levels in cord blood (P<0.001). However, such an association was not seen for AA levels. Maternal plasma omega 3 and omega 6 fatty acids were positively associated with the respective milk fatty acids (P<0.01). Conclusions: Our results indicate that milk long-chain polyunsaturated fatty acids (LCPUFA) status reflects the concentrations of maternal LCPUFA in women delivering babies at term. Improving the maternal LCPUFA status throughout pregnancy and lactation may improve the milk LCPUFA status and ultimately benefit the infant.

High Maternal Plasma Antioxidant Concentrations Associated with Preterm Delivery

Background/Aims: Our earlier study has shown that increased maternal oxidative stress and reduced antioxidants like vitamin E and C play an important role in fetal growth in preeclampsia. However, the role of antioxidants and their effects on gestation and birth outcome in normotensive pregnancies are not conclusive. The present study examined plasma malondialdehyde as a marker of oxidative stress and antioxidant concentrations (vitamins E and C) in maternal as well as in cord blood samples in normotensive women who delivered both preterm and at term. Methods: 140 normotensive pregnant women were recruited at Bharati Medical Hospital, Pune, India, during the year 2007. Maternal and cord samples were examined for oxidative stress levels and vitamin C and E concentrations in women who delivered preterm (n = 40) and at term (n = 100). Mean values were compared with those of women delivering at term using the t test. Results: Increased (p < 0.05) oxidative stress was seen in preterm mothers as well as in cord samples. Preterm mothers had higher vitamin C concentrations (p < 0.05), and these were positively associated with oxidative stress (p = 0.02). Vitamin E levels were comparable between groups. Conclusions: Increased maternal circulating vitamin C concentrations and increased oxidative stress are associated with preterm delivery.

Long-chain polyunsaturated fatty acid composition of breast milk in pre-eclamptic mothers.

Background: Maternal fatty acid nutrition during pregnancy and lactation determines the transfer of long-chain polyunsaturated fatty acids via the placenta and through human milk. Neural maturation of breast-fed infants is known to be linked to breast-milk long-chain polyunsaturated fatty acid concentrations. In spite of this, the fatty acid composition of breast milk in pre-eclamptic mothers is poorly understood. Objectives: To compare the fatty acid composition of breast milk of pre-eclamptic (n = 45) with normotensive (n = 85) mothers and examine the association of breast-milk fatty acids with plasma fatty acids. Methods: Milk and plasma fatty acid methyl esters were prepared and analyzed by the modified method of Manku and colleagues using gas chromatography. Results: Docosahexaenoic acid (DHA) concentrations were significantly increased (p < 0.01) in breast milk in spite of lower maternal plasma DHA concentrations (p < 0.05) in pre-eclamptic women. However, there was no difference in arachidonic acid levels between groups in spite of reduced maternal plasma arachidonic acid levels. Conclusions: The data suggest that in pre-eclampsia, the relation between plasma and milk DHA is altered. The resulting higher milk DHA concentrations are beneficial for infants.

Nerve growth factor, birth outcome and pre-eclampsia

The present study compares nerve growth factor (NGF) levels between preeclamptic (PE) (n = 86) and normotensive (NT) women (n = 105) and their associations with blood pressure and infant size. Maternal plasma NGF levels were reduced (p < 0.05) in the PE group as compared to the NT group. Furthermore, NGF levels were reduced in PE mothers delivering low birth weight babies (LBW) as compared to NT mothers delivering LBW babies. Maternal NGF levels were negatively (p = 0.029) associated with blood pressure in preeclamptic mothers. Cord NGF levels were negatively associated (p = 0.026) with birth weight in the normotensive group.

Differential Regulation of Brain-Derived Neurotrophic Factor in Term and Preterm Preeclampsia

Our earlier studies in preeclampsia (PE) suggest a causal relationship between altered angiogenic factors and birth outcomes. Recent studies suggest that brain-derived neurotrophic factor (BDNF) can stimulate angiogenesis. The present study examines the levels of maternal and cord BDNF in women with PE (n = 106; full term [n = 60] and preterm [n = 46]) and normotensive women (n = 95; control) delivering at term. Maternal BDNF levels were lower (P < .05) in women with PE when compared to normotensive women. Cord BDNF levels were higher (P < .01) in women with PE delivering at term, while it was lower (P < .01) in women delivering preterm. Maternal BDNF levels were negatively associated with systolic and diastolic blood pressure (P < .01 for both). Our data for the first time suggest a possible role for BDNF in the pathophysiology of PE. Differential regulation of cord BDNF levels in preterm PE suggests a need to follow-up children to assess the neurodevelopmental effects in later life.

Higher levels of brain derived neurotrophic factor but similar nerve growth factor in human milk in women with preeclampsia

Children born to mothers with preeclampsia have consistently been suggested to be at risk for cognitive and behavioral disorders in later life. Breastfeeding is said to be associated with better neurodevelopment outcomes. Our earlier studies indicated higher levels of docosahexaenoic acid (DHA) in human milk in women with preeclampsia. DHA is known to regulate the expression of neurotrophins and together they play a vital role in neurodevelopment and cognitive performance. The present study examines the levels of maternal plasma and milk neurotrophins [(nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)] in women with preeclampsia and compares them with normotensive women who served as controls. Singleton pregnant women diagnosed with preeclampsia (n = 72) and controls (n = 102) were recruited for this study from Bharati Hospital, Pune. Plasma and milk samples were analyzed for NGF and BDNF levels using the Emax Immuno Assay System using promega kits. Maternal plasma NGF and BDNF levels were lower (p < 0.01 for both) in women with preeclampsia as compared to the control women. Milk NGF levels were similar while milk BDNF levels were higher (p < 0.05) in the preeclampsia group as compared to controls. Plasma NGF levels were positively correlated with milk NGF levels in the control group. Our results indicate the differential regulation of milk NGF and BDNF levels in women with preeclampsia. The present study suggests a role for both NGF and BDNF in human milk for postnatal brain development. Further studies need to examine the associations of DHA and BDNF in human milk with cognition at later ages.

Associations of long-chain polyunsaturated fatty acid concentrations with birth outcome in term Indian mothers and their neonates.

The purpose of this study was to examine the maternal and cord long‐chain polyunsaturated fatty acid (LCPUFA) concentrations and their associations with birth outcome in term deliveries. Pregnant women (n = 253) delivering at term were divided into two groups based on their babies birth weights (1) normal birth weight (NBW), that is, ≥2.5 kg (n = 190) and (2) low‐birth weight (LBW), that is, <2.5 kg (n = 63). Each group is further divided into two groups according to the babys sex, that is, male NBW (M‐NBW), female NBW (F‐NBW), male LBW (M‐LBW), and female LBW (F‐LBW) groups. Maternal plasma docosahexaenoic acid and erythrocyte arachidonic acid (AA) levels were lower (P < 0.05 for both), while cord plasma docosahexaenoic acid and erythrocyte AA levels were higher (P < 0.05 for both) in LBW group when compared to the NBW group. Maternal erythrocyte AA levels were positively associated with birth weight (P = 0.001), while cord plasma docosahexaenoic acid levels were negatively (P = 0.05) associated with birth weight. Reduced maternal and increased cord LCPUFA levels exist in mothers delivering LBW babies, especially in mothers delivering female babies, indicative of sex‐specific effects. Am. J. Hum. Biol., 2011.